Etanercept-Induced Myelopathy in a Pediatric Case of Blau Syndrome

Abstract

Blau syndrome is a rare autoinflammatory disorder within the group of pediatric granulomatous diseases. Mutations in nucleotide-binding oligomerization domain 2 (NOD2/CARD15) are responsible for this condition, which has an autosomal dominant pattern of inheritance and variable expressivity. The clinical picture includes arthritis, uveitis, skin rash, and granulomatous inflammation. Central nervous system involvement is seldom reported, although some isolated cases of seizures, neurosensorial hearing loss, and transient cranial nerve palsy have been described. Treatment consists of nonsteroidal anti-inflammatory drugs, corticosteroids, and immunosuppressive agents, among which anti-tumor-necrosis-factor-alpha (TNF-α) biologic agents, such as etanercept, play an important role. Among the major adverse effects of TNF-α inhibitors, demyelinating disease, multiple sclerosis, and acute transverse myelitis have been reported in adults. We describe a case of pediatric Blau syndrome affected by etanercept-induced myelopathy, manifesting as a clinical syndrome of transverse myelitis. The patient experienced rapid recovery after etanercept was discontinued. To our knowledge, this is the first such case reported in the literature and, possibly, the one with the latest onset, following 8 years of treatment. We discuss the etiopathogenic mechanisms of this reaction and possible explanations for the imaging findings.

Blau Syndrome and Early-Onset Sarcoidosis: A Six Case Series and Review of the Literature

“…24 The patients treated with biological therapy after 2000 have been summarized in Table 3. [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] Although our patients with predominantly articular symptoms responded to methotrexate and TNF inhibitor therapies, we could not achieve remission with TNF, interleukin (IL)-6, or IL-1 inhibitor therapies in patient 4. In addition, remission was achieved with a low dose steroid and canakinumab treatment for patient 1 without articular symptoms.…”

Tumor Necrosis Factor Inhibitors Provide Longterm Clinical Benefits in Pediatric and Young Adult Patients with Blau Syndrome

“…TNF-α inhibition with IFX or ADA has shown successful results in a few patients with Blau syndrome 7,8 , which is in agreement with our findings. In contrast, IFX, ADA, or ETN were inefficacious in several patients 1 ; further, ETN-induced myelopathy has been reported in a pediatric patient with Blau syndrome 9 . Use of the IL-6 receptor inhibitor TCZ has not been reported in patients with Blau syndrome.…”

Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis

“…In addition, canakinumab, the human monoclonal IgG 1 that selectively neutralizes IL-1β, at the dosage of 2 mg/kg every 4 weeks, has had brilliant results in a 4-year-old boy diagnosed with EOS and presenting with refractory panuveitis: in this patient almost all of the upregulated transcripts of innate immunity-related genes normalized after the first canakinumab administration [94]. A variable response to different treatments using the same cytokine target seems to support the role of NF-κB in BS and EOS pathogenesis [59,84,94], demonstrating the complex heterogeneous biochemical background behind both familial and sporadic forms of the disease. However, the number of BS and EOS patients is still low, making it difficult to draw firm and definite conclusions.…”

“…Neurological diseases have been reported both in BS [30,47] and EOS [60,72], especially cranial neuropathies. Acute transverse myelitis occurred in a child with BS under treatment with etanercept [84]. Heart involvement is rare, mostly associated with BS, in the form of congestive heart failure [71] or hypertrophic cardiomyopathy [60,64,72].…”